Development Of Primary Hyperparathyroidism Research Articles

BROWN TUMOR OF BONE AS INITIAL MANIFESTATION OF PRIMARY HYPERPARATHYROIDISM

Primary hyperparathyroidism (PHPT) is characterized with primary hyperproduction of parathyroid hormone (PTH) by affected parathyroid glands and with a corresponding increase in concentration of extracellular calcium. Long-term development of PHPT through decades leads to calcium-related symptoms and distinct changes in the skeleton, kidneys, digestive tract and other organs. In the clinical picture of PHPT, granulomatous pseudo-tumors in bones are observed as a rare manifestation of the disease – these lesions, which could imitate malignancy, are called «brown tumors». The present publication that goes into details about a clinical diagnosis, in which a brown tumor became the primary manifestation of PHPT, may be useful for physicians across various fields.

Lower Vitamin D Levels in Surgical Hyperparathyroidism versus Thyroid Patients

Low vitamin D levels have been shown to be associated with primary hyperparathyroidism, but it is unclear whether vitamin D deficiency may be an etiologic factor in the development of primary hyperparathyroidism. To investigate this, we compared preoperative vitamin D levels of patients undergoing surgery for primary hyperparathyroidism with those of patients undergoing surgery for benign thyroid disease. With Institutional Review Board approval, data were collected prospectively on patients undergoing parathyroidectomy or thyroidectomy by one surgeon between March 2006 and July 2011. Patients were excluded if they underwent simultaneous thyroid and parathyroid surgery, had secondary or tertiary hyperparathyroidism, if no preoperative vitamin D level was measured, or if they took vitamin D supplements. Inclusion criteria were met by 219 patients who underwent parathyroidectomy and 186 patients who underwent thyroid surgery. Patient age, sex, race, and preoperative vitamin D levels (vitamin D 25-OH; normal, 32 to 100 pg/mL) were collected. Statistical analysis was performed using linear regression. Vitamin D levels were significantly lower in the parathyroid group compared with the thyroid group (23.8 vs 28.5 pg/mL; P < 0.001). This difference was also observed after adjustment for age, sex, and race with a mean difference of 4.87 pg/mL (P < 0.001). Statistically significant associations between lower vitamin D levels and patients younger than 50 years (P = 0.048), male sex (P = 0.03), and nonwhite race were identified (P < 0.001). Patients with primary hyperparathyroidism are more likely to have lower vitamin D levels than a control surgical population. Further study is needed to determine whether low vitamin D levels may be an etiologic factor associated with the development of hyperparathyroidism.

Does calcium intake influence the development of primary hyperparathyroidism?

Does calcium intake influence the development of primary hyperparathyroidism?

Prevalence of Primary Hyperparathyroidism and Impact on Bone Mineral Density in Elderly Men: MrOs Sweden

Age and sex are of importance in the development of primary hyperparathyroidism (PHPT), and the disease is most common in postmenopausal women. Skeletal complications are well known at an advanced stage of PHPT, although the impact on bone mineral density (BMD) is evident in patients with mild disease. This study examines the prevalence of PHPT in elderly men and its impact on BMD. Calcium homeostasis and BMD, measured by dual X-ray absorptiometry, were evaluated in 3014 men ages 69 to 81 years in the MrOS-Sweden cohort. Individuals with a low glomerular filtration rate (<21 ml/min/1.73 m2) and vitamin D deficiency (<50 nmol/l) were excluded. Among the remaining subjects, PHPT was assumed in subjects with above-normal albumin-adjusted serum (s)-calcium and plasma intact parathyroid hormone (p-iPTH) levels (PHPT group). BMD was compared between the PHPT group and men without PHPT. Subjects with inappropriately elevated iPTH (IEP group), based on both s-calcium (2.34 mmol/l) and iPTH (4.24 pmol/l) levels being above the median level, were compared to the rest of the cohort. The prevalence of PHPT was estimated to be 0.73%. The mean BMD in the total hip and femoral neck was lower in the PHPT group than in the PHPT controls. Significantly lower BMD (p<0.05) was seen in the IEP group (total hip and lumbar spine). Elderly men appear to have a lower prevalence of PHPT than women at the same age. The impact of disturbed calcium homeostasis on BMD was also evident in this population group.

Neoplasia endócrina múltipla tipo 1: diagnóstico clínico, laboratorial e molecular e tratamento das doenças associadas

Multiple endocrine neoplasia (MEN) syndromes include types 1 (MEN 1) and 2 (MEN 2), von Hippel-Lindau syndrome, neurofibromatosis type 1 and Carney complex. These are complex genetic syndromes caused by activation or inactivation of different types of genes known to be involved in the regulation of cell proliferation. In this review we will discuss the clinical manifestations and management of the MEN 1 syndrome as well as the genetic screening of potential MEN 1 gene carriers. MEN 1 is a hereditary syndrome, transmitted in an autosomic dominant fashion and caused by an inactivating mutation of the MEN 1 gene, characterized by the development of primary hyperparathyroidism, islet cell tumors and pituitary adenomas. In addition, these patients can present with cutaneous manifestations such as angiofibromas and collagenomas, and can develop other neoplastic manifestations including carcinoids, thyroid tumors, adrenal adenomas, lipomas, pheochromocytomas and meningiomas. The MEN 1 gene encodes a peptide which is a tumor suppressor gene called menin. Several studies have demonstrated its importance in regulation of cell proliferation and have confirmed its role in the pathogenesis of the MEN 1 syndrome. The discovery of the MEN 1 gene and the genetic analysis of MEN 1 patients have resulted in earlier diagnosis and treatment of asymptomatic carriers which can potentially result in a longer survival of these patients. Further investigation of the function and signaling pathways of the menin protein will hopefully offer therapeutic alternatives to patients with malignant progression of MEN 1-related tumors and also result in improved survival.

The vitamin D receptor (VDR) start codon polymorphism in primary hyperparathyroidism and parathyroid VDR messenger ribonucleic acid levels.

Vitamin D regulates parathyroid cell proliferation and secretion of PTH. Increased prevalence of the polymorphic vitamin D receptor (VDR) alleles b, a, and T has been reported in sporadic primary hyperparathyroidism (PHPT), suggesting that these genetic variants may predispose to the disease. Recently, another polymorphism in the VDR gene was related to bone mineral density, and this VDR-FokI polymorphism causes different lengths of the VDR, implying possible functional consequences. The VDR-FokI polymorphism was studied in 182 postmenopausal women with sporadic PHPT and in matched controls. No significant differences in distribution of the VDR-FokI genotypes could be detected between the groups, although there was a tendency toward overrepresentation of the F allele in the PHPT patients (P = 0.05). There were no significant associations with age, serum calcium, serum PTH, bone mineral density, or parathyroid tumor weight. The VDR genotypes were unrelated to VDR and PTH messenger ribonucleic acid levels in the parathyroid adenomas of 42 PHPT patients. In 23 PHPT patients, the Ca2+-PTH set-points were determined in vivo and were unrelated to the VDR alleles. We suggest that the VDR-FokI polymorphism has at most a minor pathogenic importance in the development of PHPT.

Melatonin, cortisol, prolactin, and calcitonin secretion in primary hyperparathyroidism before and after surgery.

The aim of the present study was to determine the diurnal secretion of melatonin, cortisol, prolactin, and calcitonin during chronic parathyroid hormone-dependent hypercalcemia. Eight women, aged 40-76 years, with primary hyperparathyroidism (PHPT) were studied before and after surgical removal of a parathyroid adenoma. The hormone concentrations in blood were determined at 08, 12, 16, 22, 02, 04, and 06 h. Concomitantly, the excretion of melatonin and cortisol in urine between 07-19 h and 19-07 h, and the clearance of calcium and creatinine were measured. Nyctohemeral serum prolactin and calcitonin were unaffected by moderate parathyroid hormone-dependent hypercalcemia. In contrast, serum cortisol and melatonin were significantly higher during active disease than after surgical cure. Mean 24-h variation of serum cortisol was 349 +/- 34 nmol/liter vs. 223 +/- 17 nmol/liter and mean serum melatonin was 0.13 +/- 0.04 nmol/liter vs. 0.06 +/- 0.02 nmol/liter. Endogenous creatinine clearance was similar before and after surgery, while the clearance of melatonin and cortisol significantly increased after surgery, indicating an increased tubular reabsorption of both hormones during active disease. Fasting morning glucose concentrations were also significantly decreased after successful surgery, 6.1 +/- 0.6 vs. 5.2 +/- 0.5 mmol/liter. It is suggested that the relative hypercortisolism may be the cause of the glucose intolerance in primary hyperparathyroidism. Three to 4 months after surgical cure the serum melatonin levels were significantly lower than those seen in age-matched controls, indicating a melatonin insufficiency in patients successfully treated for PHPT. The meaning of this finding is not yet understood but might be of importance in the development of primary hyperparathyroidism.

Calcium Status Following Neck Radiation Therapy in Hodgkin's Disease

Substantial evidence links the development of primary hyperparathyroidism with a medical history of neck radiation therapy for benign disease. This report concerns 220 patients with Hodgkin's disease seen at The University of Texas M. D. Anderson Hospital, Houston, treated with neck irradiation. Serum calcium levels had been analyzed two to 22 years after radiotherapy. Hyperparathyroidism was confirmed at surgery in one patient with hypercalcemia 15 years after radiotherapy. However, the maximum follow-up was 22 years and in a reported series the mean interval between irradiation and the development of hyperparathyroidism has ranged from 29 to 47 years. We conclude that patients who have received neck radiation therapy for malignant disease are not at an increased risk for the development of hyperparathyroidism in the first two decades following treatment but should continue to be screened for this development in subsequent decades.

Evaluation of parathyroid function in patients with hypergastrinaemia and pernicious anaemia.

In order to evaluate the possible causal relationship between raised serum gastrin levels and the development of primary hyperparathyroidism (HPT) which is suggested from experimental studies we evaluated parathyroid function in a group of 32 patients with hypergastrinaemia and pernicious anaemia. The values for serum calcium and parathyroid hormone were determined as well as the fasting urinary excretions of cyclic AMP and calcium. There was no relationship between the serum gastrin levels and any of the other studied parameters and there was no consistent pattern suggesting parathyroid hyperfunction. A retrospective analysis of hospital records from 441 patients operated for primary HPT showed a prevalence of pernicious anaemia of 1.8%. This figure is higher than that found in the unselected age-matched population (0.31%). However, taken together this study does not support the hypothesis that hypergastrinaemia is of particular importance for the pathogenesis of primary HPT.